This invention relates to the field of weight control, and more particularly to a novel method for inhibiting weight gain in a mammal by administration to the mammal of a long acting weight control agent comprising a nonpeptide opioid antagonist and another moiety.
Previous studies have suggested that endogenous opioids may be involved in the control of feeding and appetite. See, for example, H. N. Bhargava, "Opiate Agonists and Antagonists: Pharmacological, Behavioral, and Neurochemical Effects of Stereoisomers," in "CRC Handbook of Stereoisomers: Drugs in Psychopharmacology", D. F. Smith, Ed., CRC Press, Boca Raton, Florida, 1984, pp. 401-439, and the references cited therein. In particular, it has been demonstrated that the administration of naloxone reduces food intake in animals (for example, mice, rats, guinea pigs, squirrel monkeys) and humans by blockage of opiate receptors, Bhargava, supra; Herman and Holtzman, Life Sci., 34, 1-12 (1984). Yim and Lowy, "Opioids, Feeding, and Anorexias", Federation Proceedings Vol. 43, 14, pp. 2893-2897 (November 1984), reported that administration of the opioid antagonists naloxone and naltrexone were effective in suppressing feeding that had been induced by administration of 2-deoxy-D-glucose. The latter paper further reported that naloxone was effective in reversing anorexia induced by opioid agonists such as morphine.
In the development of compositions and methods for weight control, there is a need for anorexic or other weight control agents which are long lasting, generally non-toxic, and substantially free of any other adverse side effects. There is a particular need for compositions which may be administered orally to produce persistent control of weight without toxic effects on the recipient.
Hahn, Pasternak et al, J. Neuroscience, 2, 572-576 (1982), discovered that the opiate antagonist naloxone azine has a long lasting effect, i.e, that it is removed only very slowly after having been bound to the sites of opioid receptors. However, Hahn et al did not disclose any possible use of naloxone azine as a weight control agent.